Exercise Intolerance in Renal Failure

NCT01356966 | Completed Phase 2 Results

• 2 other identifiers: IRB00019181K23HL098744
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 2

Brief Summary

Patients with chronic kidney disease have profound exercise intolerance which contributes to an increased risk of cardiovascular disease. The investigators have found that chronic kidney disease patients have an exaggerated increase in blood pressure during certain forms of exercise that could certainly contribute to exercise dysfunction as well as cardiovascular risk. The investigators will test the mechanisms underlying this exaggerated blood pressure response, as well as the potential benefits of short-term tetrahydrobiopterin (BH4) with folic acid on both exercise dysfunction and cardiovascular risk factors in chronic kidney disease. The investigators will test whether short-term treatment with tetrahydrobiopterin (BH4), a cofactor for nitric oxide, together with folic acid improves inflammation, vascular health, and adrenaline levels, both at rest and during exercise in chronic kidney disease.

Conditions

Kidney Failure, Chronic

Outcome Measures

Primary Outcomes (1)

• Change in Resting Muscle Sympathetic Nerve Activity (MSNA)

  Baseline, 12 weeks

Secondary Outcomes (2)

• Change in Mean Central Augmentation Index (AIx)

  Baseline, 12 weeks

• Change in Heart-rate-corrected Augmentation Index (AIx)

  Baseline, 12 weeks

Study Arms (2)

Tetrahydrobiopterin + Folate

EXPERIMENTAL

Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive Tetrahydrobiopterin (6R-BH4) 200 mg twice daily and folic acid 1 mg daily

Drug: Tetrahydrobiopterin; Dietary Supplement: Folate

Placebo + Folate

PLACEBO COMPARATOR

Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive 2 placebo pills twice daily and folic acid 1 mg daily

Drug: Placebo; Dietary Supplement: Folate

Interventions

Tetrahydrobiopterin DRUG

Tetrahydrobiopterin (BH4) 200 mg PO BID for 12 weeks

Also known as: Kuvan

Tetrahydrobiopterin + Folate

Placebo DRUG

2 placebo pills PO BID for12 weeks

Placebo + Folate

Folate DIETARY_SUPPLEMENT

Folate 1 mg daily for 12 weeks

Also known as: Folic Acid

Placebo + Folate; Tetrahydrobiopterin + Folate

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• chronic kidney disease (CKD) stages I, II, and III and do not regularly exercise
• \. CKD Stages I, II, and III will be defined as reduction in estimated glomerular filtration rate (eGFR) to 30-59 cc/minute as calculated by the Modification of Diet in Renal Disease (MDRD) equation, or an eGFR\>60 cc/minute with proteinuria greater than 500 mg/g of Creatinine or 500 mg per 24 hours.
• willing and able to cooperate with the protocol
• CKD patients must have stable renal function (no greater than a 20% reduction in eGFR over the prior 3 months)
• controls will be matched for age, gender, race, and hypertensive status.

You may not qualify if:

• severe CKD (eGFR\<30 cc/minute)
• drug or alcohol abuse
• diabetes
• any serious systemic disease that might influence survival
• severe anemia with hgb level \<10 g/dL
• clinical evidence of congestive heart failure or ejection fraction below 35%
• any history of past myocardial infarction or cerebrovascular accident
• symptomatic heart disease determined by electrocardiogram, stress test, and/or history
• treatment with central alpha agonists
• uncontrolled hypertension with BP greater than 160/90 mm Hg
• low blood pressure with BP less than 110/60
• history of nephrolithiasis
• pregnancy or plans to become pregnant
• treatment with vitamin C within the past 3 months
• hepatic enzyme concentrations greater than 2 times the upper limit of normal

Sponsors & Collaborators

• Emory University: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Atlanta VA Medical Center

Decatur, Georgia, 30033, United States

Location

Related Publications (1)

• Lin AM, Liao P, Millson EC, Quyyumi AA, Park J. Tetrahydrobiopterin ameliorates the exaggerated exercise pressor response in patients with chronic kidney disease: a randomized controlled trial. Am J Physiol Renal Physiol. 2016 May 1;310(10):F1016-25. doi: 10.1152/ajprenal.00527.2015. Epub 2016 Mar 9.

  PMID: 26962106 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

sapropterin; Folic Acid

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Jeanie Park
• Organization: Emory University

jeanie.park@emory.edu

404-727-1386

Study Officials

• Jeanie Park, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: May 18, 2011
• First Posted: May 20, 2011
• Study Start: May 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: June 1, 2015
• Results First Posted: June 1, 2015

Record last verified: 2015-05

Locations

US (2)